Estrogen, the Brain, and Mood

Your Hormones and Brain Are Always in Conversation

Written by: Dr. Madeleine Clark, ND MSCP

From your first period to menopause, your brain and hormones are in constant dialogue. Changes in estrogen levels influence far more than your reproductive system; they shape brain chemistry, cognitive function, and mood regulation.

For some people, these changes pass with little disruption. For others, they can trigger intense mood symptoms such as irritability, anxiety, brain fog, or depression. The difference often comes down to sensitivity to hormonal change — something researchers call a “window of vulnerability.”

💡 If your main concern is depression or anxiety in the menopause transition, read my article on mood changes in perimenopause for a deeper dive into treatment options and whole-person care.

Where the Brain Feels Estrogen’s Impact

Estrogen receptors are found throughout the brain, including in regions tied to mood and cognition:

  • Prefrontal cortex — decision-making, emotional regulation, and attention.

  • Hippocampus — memory, learning, and stress resilience.

Through these receptors, estrogen can:

  • Boost serotonin and noradrenaline — neurotransmitters that stabilize mood.

  • Inhibit monoamine oxidase, the enzyme that breaks down serotonin.

  • Increase tryptophan availability, the raw material for serotonin production.

  • Stimulate brain-derived neurotrophic factor (BDNF), which supports brain cell growth and repair.

💡 For a deeper dive into BDNF and mood regulation, check out our depression and brain health article.

The Role of Hormone Fluctuation — Not Just Decline

During the menopause transition, estrogen doesn’t just slowly go down — it can swing dramatically higher or lower than in a typical menstrual cycle. These ups and downs can affect brain chemicals like serotonin, which support mood, reduce inflammation, and protect brain cells.

Some people are especially sensitive to these changes. In one study, about 1 in 5 women had more depressive symptoms when estrogen rose or when it fell — meaning either direction could trigger mood changes.

This sensitivity is also seen in PMS, PMDD, and postpartum depression, where both increases and decreases in estrogen can set off symptoms.

Other brain chemicals, called neurosteroids (like allopregnanolone and DHEA-S), also shift with estrogen changes. When these are out of balance, it can affect the brain’s calming system (the GABA pathway), making mood symptoms more likely.

Why this matters for you: If your mood feels unstable during midlife, even if you’ve never had depression before, it could be your brain’s sensitivity to hormonal swings, not just the overall drop in estrogen.

Life Stages Where Mood Vulnerability Spikes

Because estrogen plays such a big role in brain function, large fluctuations or rapid declines can increase mood symptoms in some people.

PMS and PMDD

  • PMDD significantly increases the risk for postpartum depression (Cao, 2020).

  • This connection highlights how hormone sensitivity often shows up at multiple stages in life.

Postpartum

  • Estrogen drops dramatically after childbirth, contributing to postpartum mood changes, especially in those with a history of hormone sensitivity.

Perimenopause

Surgical Menopause and Hysterectomy

  • Bilateral oophorectomy before menopause increases lifetime risk of depression and anxiety.

  • Hysterectomy without ovarian conservation raises depression risk by 44%; with ovarian conservation, by 20%.

  • These associations persist even after controlling for lifestyle and socioeconomic factors.

What This Means for Treatment

Because hormone-related mood changes are complex, treatment needs to be individualized and multi-layered:

  • Medical supports — Antidepressants remain a mainstay for many, and hormone therapy may be considered as an adjunct in select cases.

  • Therapy — CBT, ACT, or interpersonal therapy can help build resilience and coping skills.

  • Lifestyle strategies — Nutrition, exercise, sleep hygiene, and stress management to keep the brain adaptable and reduce inflammation.

  • Targeted supplementation — Support neurotransmitter production and protect brain health.

The Takeaway

Estrogen is more than a reproductive hormone — it’s a key player in brain health. For those sensitive to hormonal change, fluctuations at any stage; PMS, postpartum, perimenopause, or after surgery, can be a trigger for mood symptoms.

I’m Dr. Madeleine Clark, ND and Menopause Society Certified Practitioner. I help women navigate hormone-sensitive mood changes with evidence-based care that blends medical, nutritional, and lifestyle strategies.

Book your appointment today to start your personalized brain–hormone health plan.

Madeleine Clark